Cryoglobulins are abnormal proteins in the blood. If you have cryoglobulinemia (kry-oh-glob-u-lih-NE-me-uh), these proteins clump together in the cold. This causes the plasma to become thick like maple syrup and deposit clumps in blood vessels.

Cryoglobulinemia tends to be a condition that occurs in people over 50 years of age. Most people with cryoglobulinemia won't experience symptoms. But if you have moderate to severe disease, you may experience blocked arteries and damage to your skin, joints, muscles, nerves, kidneys and liver. The course of the disease will vary, depending on the severity. Symptoms may come and go. For some people, cold temperatures may cause flare-ups.

No one knows exactly what causes cryoglobulinemia. Depending on the type you have, it may be associated with one of a number of conditions, such as hepatitis C infection, multiple myeloma and autoimmune disease.

Expertise and experience. Mayo Clinic doctors have a worldwide reputation for diagnosis and treatment of rare blood disorders, including cryoglobulinemia. Mayo specialists have been treating cryoglobulinemia for decades, attracting one of the largest patient populations with this disease.

Team approach. A multispecialty team of experts works together to develop a treatment plan based on your needs. Your treatment team may include specialists in blood (hematologists), connective tissue and arthritis (rheumatologists), liver diseases (hepatologists), the nervous system (neurologists), the kidneys (nephrologists) and other areas as needed.

Your doctor likely will start by taking your medical history and performing a physical exam. He or she will also have you undergo blood and urine tests. Your doctor may take small samples of tissue for testing (biopsy).

There are three types of cryoglobulinemia. Type 1 is usually associated with diseases of the blood, such as lymphoma and multiple myeloma. Type 2 can occur with disorders of the lymph system and chronic hepatitis C infection. Type 3 is usually associated with autoimmune disease.

Cryoglobulinemia has many possible signs and symptoms, including:

Weakness and fatigue

Joint pain (arthralgia)

Red or purple spots (purpura) on the legs or feet, which may be preceded by burning or itching

Fever

High blood pressure

Swelling of ankles and legs

Numbness, tingling or weakness in the hands or feet (peripheral neuropathy)

Skin ulcers and gangrene

Abdominal pain

The goals of treatment are to:

Address underlying causes (such as an infection)

Control inflammation

Prevent flare-ups later

Limit or prevent organ damage

Not overtreat

Treatment depends on the type, cause and severity of your cryoglobulinemia symptoms. If you don't have symptoms, your doctor may recommend careful monitoring. If you have mild to moderate symptoms, your doctor may recommend bed rest, support hose, pain medicine and avoiding cold temperatures.

You may be given prescription drugs to control symptoms and prevent flare-ups. Drugs used — alone or in combination — include:

Medicines to control inflammation. For many years, corticosteroids have been an effective choice for treating cryoglobulinemia. Long-term use of these drugs carries an increased risk of side effects, such as infection.

Medicines that suppress your immune system. You may be given man-made antibodies (monoclonal antibodies), such as rituximab (Rituxan). For some types of cryoglobulinemia, rituximab may be most effective when combined with steroids. It may also be used with chemotherapy.

Medicines that fight viral infections. If your cryoglobulinemia is related to a hepatitis C virus infection, you may be given antiviral therapy. Antivirals may be used in combination with ribavirin (Rebetol, Ribasphere).

Chemotherapy. If you have mild to moderate symptoms, you may be given low-dose chemotherapy to control the symptoms. If your symptoms are more severe, chemotherapy may be used along with blood plasma exchange (plasmapheresis).

Blood plasma exchange. If you have severe symptoms, your doctor may also recommend plasmapheresis. This treatment reduces cryoglobulins by exchanging the blood plasma (which contains much of the cryoglobulins) for donor plasma or a replacement fluid.

Mayo Clinic works with hundreds of insurance companies and is an in-network provider for millions of people. In most cases, Mayo Clinic doesn't require a physician referral. Some insurers require referrals or may have additional requirements for certain medical care. All appointments are prioritized on the basis of medical need.

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